1. Field of Invention
This application relates to processes and systems for sorting structures dispersed in a fluid and more particularly processes and systems for sorting sub-millimeter structures dispersed in a fluid using custom-shaped particles.
2. Discussion of Related Art
The contents of all references, including articles, published patent applications and patents referred to anywhere in this specification are hereby incorporated by reference.
A variety of different approaches using lithography (Madou, M. J. Fundamentals of microfabrication: The science of miniaturization. 2nd ed.; CRC Press: Boca Raton, 2002) now exist for designing and making custom-shaped sub-millimeter particles dispersed in a fluid (Hernandez, C. J.; Mason, T. G. Colloidal alphabet soup: Monodisperse dispersions of shape-designed LithoParticles. J. Phys. Chem. C 2007, 111, 4477-4480; Hernandez, C. J.; Zhao, K.; Mason, T. G. Pillar-deposition particle templating: A high-throughput synthetic route for producing LithoParticles. Soft Materials 2007, 5, 1-11; Hernandez, C. J.; Zhao, K.; Mason, T. G. Well-deposition particle templating: Rapid mass-production of LithoParticles without mechanical imprinting. Soft Materials 2007, 5, 13-31; Higurashi, E.; Ukita, H.; Tanaka, H.; Ohguchi, O. Optically induced rotation of anisotropic micro-objects fabricated by surface micromachining. Appl. Phys. Lett. 1994, 64, 2209-2210; Rolland, J. P.; Maynor, B. W.; Euliss, L. E.; Exner, A. E.; Denison, G. M.; DeSimone, J. M. Direct fabrication of monodisperse shape-specific nanobiomaterials through imprinting. J. Am. Chem. Soc. 2005, 127, 10096-10100; Brown, A. B. D.; Smith, C. G.; Rennie, A. R. Fabricating colloidal particles with photolithography and their interactions at an air-water interface. Phys. Rev. E 2000, 62, 951-960; Sullivan, M.; Zhao, K.; Harrison, C.; Austin, R. H.; Megens, M.; Hollingsworth, A.; Russel, W. B.; Cheng, Z.; Mason, T. G.; Chaikin, P. M. Control of colloids with gravity, temperature gradients, and electric fields. J. Phys. Condens. Matter 2003, 15, S11-S18). Shape-designed particles, regardless of the methods of production, will also be referred to as LithoParticles in this specification. Because the shapes of the particles can be specified and designed, these processes for making custom-shaped particles can often be adapted to make desired particle shapes that may have enhanced functionality owing to prespecified geometrical features inherent in their shapes.
The certain attractive interactions, including those created by depletion attractions, between dispersed particles in a liquid can be anisotropic and can depend on the relative orientations of the particles (Mason, T. G. Osmotically driven shape dependent colloidal separations. Phys. Rev. E 2002, 66, 060402/1-4). The discotic particles discussed by Mason in this particular article in Phys. Rev. E are not custom-shaped particles produced by any lithographic method; the method of making the particles did not involve an element of prescriptive design of their shapes. By contrast, controlled surface roughness on colloidal particles can be used to further control the strength of attractive interactions between custom-shaped particles that have been produced lithographically (Zhao, K.; and Mason, T. G. Roughness-controlled depletion attractions for directing colloidal self-assembly. Phys. Rev. Lett. 2007, 99, 268301/1-4; Zhao, K.; and Mason, T. G. Suppressing and enhancing depletion attractions between surfaces roughened by asperities. Phys. Rev. Lett. 2008, 101, 148301/1-4). Although dimer assemblies of certain particle types have been created by design, there is no element of isolation, separation, and sorting in this approach. Thus, the potential exists to design and make custom-shaped particles for interacting with and specifically binding in a form of primitive recognition with a variety of target structures dispersed in a fluid. These target structures could include biological objects, such as cells, organelles, and proteins, as well as non-biological objects, such as synthetic particles. Once bound, the aggregate of a custom shaped particle with a target structure could potentially be isolated, separated, and sorted, typically through the action of an external field or flow. This possibility would be highly useful because the formation of aggregates would occur in a highly parallel process everywhere in a dispersion that would contain both custom-shaped particles and target structures.
It would be therefore highly advantageous to take advantage of shape-specific binding by designing custom-shaped particles that can be induced to bind with one or more specific structures but not to other structures for the purposes of shape-selective recognition, identification, isolation, separation, and sorting. Past approaches in the general area have lacked the combination of custom-designing the lithographic particles for the specific desired shape and to exclude binding with other shapes along with the methods for efficiently extracting the bound objects from the other structures. It is precisely this combination that would provide a highly useful process for isolating, separating, and sorting dispersed sub-millimeter structures.
New methods for making custom-shaped colloidal particles offer unique opportunities for capturing and separating specific molecular, particulate, and cellular species in soft colloidal materials that contain a complex variety of components. An excellent example of a soft colloidal material is normal adult human blood, which can contain a wide variety of proteins, complexes, and cells in an aqueous solution at a well-regulated pH. Among the current challenges in the fields of biomedicine and nanomedicine, it is important to develop methods of efficiently separating different components and cell types in human blood with a high degree of shape and size specificity. Diagnostic methods that rely on detecting very small numbers of abnormal cells in blood are also highly desirable. Beyond detection, shape-selective separation of small numbers of abnormal cells in a viable state that would permit further study would be a major breakthrough.
Normal human peripheral blood can contain a wide variety of cell types, including band neutrophils, segmented neutrophils, basophils, eosinophils, erythrocytes (red blood cells), lymphocytes (white blood cells), monocytes, and platelets. Of these main categories of cell types, numerous sub-categories and refinements of these cell types also exist. Additional diversity in cells types and shapes can be present for human blood in diseased states, including for various disease types such as anemias and cancers. Normal human red blood cells are disk-like, readily deformable, and have biconcave dimples, and they are quite uniform in shape and size, having a low polydispersity. The size and shape of the red blood cells can even change to some degree depending upon the age of the cell and its biological history. By contrast, other cell types in human blood, such as lymphocytes, have shapes and sizes that are not disk-like. In addition to shape and size, the compositions and effective roughness of the surfaces of different cell types can likewise be potentially used to distinguish one cell type from another. (See also, U.S. application Ser. No. 12/377,773 filed Feb. 17, 2009 as a national stage application of PCT/US07/18365, titled “Customized Lithographic Particles”; U.S. application Ser. No. 12/563,907 titled “Mechanical Process for Creating Particles in a Fluid” filed Sep. 21, 2009 as a CIP of PCT/US08/03679; U.S. application Ser. No. 12/575,920 titled “Process for Creating Shape-Designed Particles in a fluid” filed Oct. 8, 2009; U.S. application Ser. No. 12/524,946 filed Jul. 29, 2009 as a national stage application of PCT/US08/01443, titled “Massively Parallel Assembly of Composite Structures using Depletion Attraction”; and PCT/US08/12832 titled “Process for Directing Assemblies of Particulate Dispersions Using Surface Roughness,” all by the same assignee as the current application and the entire contents of each of which are hereby incorporated by reference.) There thus remains a need for improved methods and systems for sorting sub-millimeter particles dispersed in a fluid.